Encouraging results for amlitelimab in atopic dermatitis

In a phase 2b study, patients with atopic dermatitis (AD) treated with the OX40 ligand inhibitor amlitelimab presented clinically meaningful improvements in the Eczema Area and Severity Index (EASI). Varying by dose regimen, EASI decreased between 51.6% and 61.5% in the study groups.

“Despite the current emergence of so many efficacious treatments for AD, there are still unmet needs particularly when it comes to really deep and durable responses,” Prof. Stephan Weidinger (University Hospital Schleswig-Holstein, Germany) stated [1]. He pointed at the OX40 pathway as a very promising AD treatment target. The phase 2b STREAM-AD (NCT05131477) trial was designed to test 5 different dosages of the OX40 ligand inhibitor amlitelimab against placebo as monotherapy in adults with moderate-to-severe AD, defined as a baseline EASI of ≥16, an Investigator’s Global Assessment (IGA) of 3 or 4, and at least 10% of affected body surface area (BSA).

STREAM-AD randomised 390 participants to a 4-weekly treatment with placebo or the study drug in 4 groups (250 mg + loading dose of 500 mg, 250 mg without a loading dose, 125 mg without a loading dose, or 62.5 mg without a loading dose). The primary endpoint was the proportion of EASI change at week 16. Follow-up of 6 more weeks completed part 1 of STREAM-AD. “Overall, this was a typical moderate-to-severe AD population,” Prof. Weidinger commented on the baseline characteristics. The mean age was 37.8 years, 43.8% were women, and the mean duration of AD was 22.3 years. Mean disease measures were EASI28.9, IGA 3.3, and BSA involved 46.2%.

At week 16, the study met its primary endpoint with statistically significant superior EASI results that equalled least mean square changes between -61.5% (250 mg plus loading dose; P<0.0001) and -51.6% (125 mg; P=0.0002) compared with 29.4% in the placebo arm. On the highest dose, for example, EASI reduction continued up to week 24 with -64.4% or -73.1%, depending on the statistical approach to categorising cases of rescue medication.

Among the secondary endpoints were achievement of IGA 0/1, EASI75, and ≥4-point reduction on the Peak Pruritus Numerical Rating Scale (PP-NRS). Apart from IGA 0/1 on 250 mg without a loading dose, all groups on amlitelimab were significantly superior over placebo in these as well.

Up to week 24, treatment-emergent adverse events occurred in 67.4% (amlitelimab) and 60.3% (placebo) of the participants, with rates of treatment discontinuation at 4.5% and 6.4%, respectively. Overall, the agent was deemed well-tolerated.

“We also started doing biomarker analyses and what we saw there was quite interesting. Across the different exposures, we not only saw a reduction of well-known type 2 markers, such as IL-13 or TARC, but we also saw a decrease of the eosinophils and a decrease of markers of other immune axes, such as IL-17 and IL-22,” Prof. Weidinger further revealed.

The second part of STREAM-AD, which includes a withdrawal/extension design for the 24-week responders and a safety follow-up until week 68, is currently ongoing.

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   1. Weidinger S. Efficacy and safety of amlitelimab (an anti-OX40 ligand antibody) in patients with moderate-to-severe atopic dermatitis: 24-week results from a Phase 2b trial (STREAM-AD). D3T01.3G, EADV Congress 2023, 11–14 October, Berlin, Germany.

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Posted on 28 November, 202322 February, 2024